Abstract
Excess stimulation of NMDA receptors by endogenous glutamate likely contributes to the neuronal cell loss associated with several types of acute brain injury in vivo (Meldrum, 1985; Rothman and Olney, 1987, Choi, 1988), including ischemia (Simon et al., 1984), hypoglycemia (Wieloch, 1985), epilepsy (Labuyere et al., 1986) and trauma (Faden and Simon, 1988). Among the experiments supporting this statement are those studying the controlled delivery of insults to dispersed neuronal and glial cells in primary culture. Demonstration that a given pharmacological manipulation is neuroprotective in such cultures establishes that a beneficial effect can be produced directly on brain parenchyma, without involvement of systemic metabolism or alterations in blood flow. While organizational features of the intact nervous system are not expressed in cell culture, many intrinsic aspects of neuronal and glial cell behavior do appear to be qualitatively preserved. In particular, basic mechanisms relevant to glutamate transmission and glutamate neurotoxicity are present in cultured brain cells.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Auer, R.N., and Siesjo, B.K., 1988, Biological differences between ischemia, hypoglycemia, and epilepsy, Ann. Neurol, 24: 699.
Bradford, H.F., Ward, H.K., and Thomas, A.J., 1978, Glutamine - A major substrate for nerve endings, J. Neurochem, 30: 1453.
Choi, D.W., 1987, Ionic dependence of glutamate neurotoxicity in cortical cell culture, J. Neurosci, 7: 369.
Choi, D.W., 1988, Glutamate neurotoxicity and diseases of the nervous system, Neuron, 1: 623.
Dunwiddie, T.V., 1985, The physiological role of adenosine in the central nervous system, Int. Rev. Neurobiol, 27: 63.
Evans, M.C., Swan, J.H., and Meldrum, B.S., 1988, An adenosine analogue, 2-chloroadenosine, protects against long term development of ischaemic cell loss in the rat hippocampus, Neurosci. Lett, 83: 287.
Faden, A.I., Demediuk, P., Panter, S.S., Vink, R., 1989, The role of excitatory amino acids and NMDA receptors in traumatic brain injury, Science, 244: 798.
Faden, A.I., and Simon, R.P., 1988, A potential role for excitotoxins in the pathophysiology of spinal cord injury, Ann. Neurol, 23: 623.
Giffard, R.G., Monyer, H., Christine, C.W., and Choi, D.W., 1989, Acidosis reduces NMDA receptor activation, glutamate neurotoxicity, and oxygen-glucose deprivation neuronal injury in cortical cultures, Brain Res., in press.
Goldberg, M.P., Monyer, H., and Choi, D.W., 1988a, Hypoxic neuronal injury in vitro depends on extracellular glutamine, Neurosci. Lett, 94: 52.
Goldberg, M.P., Monyer, H., and Choi, D.W., 1988b, Cortical neuronal injury in vitro following combined glucose and oxygen deprivation: ionic dependence and delayed protection by NMDA antagonists, Soc. Neurosci. Abstr, 14: 745.
Goldberg, M.P., Monyer, H., Weiss, J.W., and Choi, D.W., 1988c, Adenosine reduces cortical neuronal injury induced by oxygen or glucose deprivation in vitro, Neurosci. Lett, 89: 323.
Goldberg, M.P., Pham, P.C., and Choi, D.W., 1987a, Dextrorphan and dextromethorphan attenuate hypoxic injury in neuronal culture, Neurosci. Lett, 80: 11.
Goldberg, M.P., Viseskul, V., and Choi, D.W., 1988d, Phencyclidine receptor ligands attenuate cortical neuronal injury following N-methyl-D-aspartate exposure or hypoxia, J. Pharmacol. Exp. Therap, 245: 1081.
Goldberg, M.P., Weiss, J.W., Pham, P.C., and Choi, D.W., 1987b, N-methyl-D-aspartate receptors mediate hypoxic neuronal injury in cortical culture, J. Pharmacol. Exp. Therap, 243: 784.
Hamberger, A.C., Chiang, G.H., Nylen, E.S., Scheff, S.W., and Cotman, C.W., 1979, Glutamate as a CNS transmitter. I.Evaluation of glucose and glutamine as precursors for the synthesis of preferentially released glutamate, Brain Res., 168: 513.
Hayes, R.L., Jenkins, L.W., Lyeth, B.G., Balster, R.L., Robinson, S.E., Clifton, G.L., Stubbins, J.F., Young, H.F., 1988, Pretreatment with phencyclidine, an N-methyl-D-aspartate antagonist, attenuates long-term behavioral deficits in the rat produced by traumatic brain injury, J. Neurotrauma, 5: 259.
Labuyere, J., Fuller, T.A., Olney, J.W., Price, M.T., Zorumski, C., Clifford, D., 1986, Phencyclidine and ketamine protect against kainic acid-induced seizures and seizure-related brain damage, Soc. Neurosci. Abstr, 12: 344.
McIntosh, T., Soares, H., Hayes, R., Simon, R., 1988, The NMDA receptor antagonist MK-801 prevents edema and restores magnesium homeostasis after traumatic brain injury in rats, in: “Frontiers in Excitatory Amino Acid Research,” E.A. Calalheiro, J. Lehmann, and L. Turski, eds., Alan R. Liss, New York.
Meldrum, B., 1985, Possible therapeutic applications of antagonists of excitatory amino acid neurotransmitters, Clin. Sci, 68: 113.
Monyer, H., Goldberg, M.P., Choi, D.W., 1989, Glucose deprivation neuronal injury in cortical culture, Brain Res., 483: 347.
Monyer, H., and Choi, D.W., 1989, Glucose deprivation neuronal injury in vitro is modified by withdrawal of extracellular glutamine, J. Cereb. Blood Flow Metab, accepted.
Morad, M., Dichter, M., and Tang, C.M., 1988, The NMDA activated current in hippocampal neurons is highly sensitive to [H+] Soc. Neurosci. Abstr. 14: 791.
Rothman, S., 1984, Synaptic release of excitatory amino acid neurotransmitter mediates anoxic neuronal death, J. Neurosci, 4: 1884.
Rothman, S.M., and Olney, J.W. 1987, Excitotoxicity and the NMDA receptor, Trends Neurosci., 10: 299.
Schurr, A., Dong, W.Q., Reid, K.H., West, C.A., and Rigor, B.M., 1988, Lactic acidosis and recovery of neuronal function following cerebral hypoxia in vitro, Brain Res., 438: 311.
Simon, R.P., Swan, J.H., Griffiths, T., and Meldrum, B.S., 1984, Blockade of N-methyl-D-aspartate receptors may protect against ischemic damage in the brain, Science, 226: 850.
Tecoma, E.S., Monyer, H., Goldberg, M.P., and Choi, D.W., 1989, Traumatic neuronal injury in vitro is attenuated by NMDA antagonists, Neuron, 2: 1541.
Von Lubitz, D.K., Dambrosia, J.M., Kempski, O., and Redmond, D.J., 1988, Cyclohexyl adenosine protects against neuronal death following ischemia in the CAI region of gerbil hippocampus, Stroke, 19: 1133.
Weiss, J., Goldberg, M.P., and Choi, D.W., 1986, Ketamine protects culturedneocortical neurons from hypoxic injury, Brain Res., 380: 186.
Wieloch, T., 1985, Hypoglycemia-induced neuronal damage prevented by an N-methyl-Daspartate antagonist, Science, 230: 681.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1990 Springer Science+Business Media New York
About this chapter
Cite this chapter
Choi, D.W., Monyer, H., Giffard, R.G., Goldberg, M.P., Christine, C.W. (1990). Acute Brain Injury, NMDA Receptors, and Hydrogen Ions: Observations in Cortical Cell Cultures. In: Ben-Ari, Y. (eds) Excitatory Amino Acids and Neuronal Plasticity. Advances in Experimental Medicine and Biology, vol 268. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5769-8_55
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5769-8_55
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5771-1
Online ISBN: 978-1-4684-5769-8
eBook Packages: Springer Book Archive